admin July 13th, 2007
The BMJ has published the WISDOM Trial of HRT in postmenopausal women aged 50 to 69 years-of-age (mean age 62.8 SD 4.8).
Key points:
Combined hormone therapy (n=2196) was compared with placebo (n=2189):
- significant increase in the number of major cardiovascular events (7 v 0, P=0.016)
- significant increase in venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60))
- no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)).
Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes:
- no significant differences.
The study authors argue that this trial is consistent with the Womens’ Health Initiative trial, showing increased risks associated with HRT when used in older post-menopausal women. It is less useful in casting light on the risk to women who are younger and who are using HRT to deal with menopausal symptoms. An accompanying editorial argues that:
So postmenopausal hormone therapy has come full circle.9 It was originally used to treat menopausal symptoms, and now the indications for use are again hot flushes, night sweats, and vaginal dryness. It is the best treatment we have at present for these symptoms. Hot flushes and night sweats are mostly self limiting, and current advice recommends short term use with the lowest dose needed for relief of symptoms. Healthy women in early menopause are at a low absolute risk whether they take hormones or not, and they are unlikely to face substantially increased risks when using hormones for a few years.
Long term use of hormone replacement therapy to prevent chronic disease is no longer recommended, because available randomised evidence shows that the negative outcomes outweigh the positive benefits.
admin June 26th, 2007
Restrictions have been placed on the use of piroxicam. First prescriptions should not be for longer than 2 weeks and it can only be used in patients with osteoarthritis, rheumatoid arthritis, or, ankylosing spondylitis as second line treatment.
The European Medicines Agency (EMEA) has recommended restrictions on the use of piroxicam containing medicinal products because of the risk of gastrointestinal side effects and serious skin reactions. The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that piroxicam should no longer be used for treatment of short-term painful and inflammatory conditions.
Piroxicam can still be prescribed for the symptomatic relief of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. However it should not be the first choice of non-steroidal anti-inflammatory drug (NSAID) treatment in these conditions.
More at EMEA in PDF format.
Also see:
EMEA Question and Answer sheet.
MHRA statement.
admin June 20th, 2007
Over the past month the New England Journal of Medicine has published a meta-analysis and an interim results paper of the RECORD study concerned with the cardiovascular safety of rosiglitazone. There is coverage of both the meta-analysis and the trial data at prescriber.org.uk
Currently the MHRA and EMEA are not taking any action based on these results. Avandia is a centrally licensed drug, and therefore the European Medicines Agency has issued a statement about the cardiac safety of rosiglitazone. Patients are advised not to stop their treatment with rosiglitazone, but should discuss any concerns about their medication at their next routine appointment with the doctor. The statement is available at the MHRA website.
admin June 9th, 2007
The Lancet [registration required] reports on a case of sumatriptan-induced sulfhaemoglobinaemia:
In October, 2005, a 42-year-old man presented to our hospital, having developed a compartment syndrome in both lower legs. He was a smoker; his medical history included migraine. His regular medications were sumatriptan, which he had been taking at a dose of 200 mg per day, for several months, diclofenac, and zopiclone.
[...]
several attempts to insert an indwelling radial-arterial catheter yielded dark, greenish-black blood. Eventually, the catheter was advanced, and pressure transduction confirmed arterial placement. The displayed SpO2 was 96% on supplemental oxygen (inspired oxygen fraction [FIO2], 0.5). A sample of the greenish-black blood was sent to the laboratory for co-oximetry. The oxygen saturation (SaO2) was 94%, and the oxygen partial pressure (PaO2) 135 mm Hg. The methaemoglobin concentration was within the normal range, at 1·17 g/L (0·9%), as was the carboxyhaemoglobin concentation—but the analyzer displayed an alert to the presence of sulfhaemoglobin. Quantitative analysis (Beckman DU65 Spectrophotometer, Beckman Coulter, Mississauga, Canada) revealed a sulfhaemoglobin concentration of 2 g/L. The patient recovered uneventfully, and stopped taking sumatriptan after discharge. When seen 5 weeks after his last dose, he was found to have no sulfhaemoglobin in his blood.
M Flexman A, Del Vicario G, Schwarz SKW. Dark green blood in the operating theatre. The Lancet 2007; 369: 1972
The BBC also reports on the story.
admin February 19th, 2007
FDA notified healthcare professionals of the results from a large clinical trial evaluating use of an erythropoiesis-stimulating agent (ESA) to treat anemia in cancer patients not receiving chemotherapy. In this study, patients received either Aranesp, an ESA, according to the approved dosing regimen or placebo. Patients treated with Aranesp had a higher death rate and no reduction in the need for transfusions compared to those treated with placebo. The findings in the Aranesp study may apply to other ESAs. Additionally, the findings show that treating anemic cancer patients not currently on chemotherapy with an ESA may offer no benefit and may cause serious harm.
FDA.
admin February 2nd, 2007
The FDA report and Genentech report on an ongoing study (SAILOR) which confirmed the higher incidence of stroke associated wtih ranibizumab with a 0.5 mg dose group compared to the 0.3 mg dose group (1.2% versus 0.3%, respectively; P=0.02) which used in patients with neovascular (wet) age-related macular degeneration who received intravitreal Lucentis.
admin December 18th, 2006
The BMJ report on the HARM study, published in the Netherlands:
The hospital admissions related to medication (HARM) study found that 41 000 hospital admissions a year in the Netherlands were caused either by the incorrect use of or adverse reactions to drugs (www.nvza.nl).
These admissions accounted for 5.6% of acute admissions and were twice as likely to involve patients older than 65 years.
Almost half—19 000 admissions—were deemed “possibly avoidable” and cost the health services 85m euros (£57m; $112m) a year. They were thought to play a part in an estimated 1254 deaths a year.
This first empirical study into the safety of medicines in the Netherlands screened all acute admissions in 21 hospitals over 40 days to see whether the reasons for admissions included drug related problems.
Patients identified as being at risk were those who had failed to take their medicines properly; had reduced competence; took more than five different drugs; and had more than one medical condition, in particular kidney failure.
More information is available here.
admin December 18th, 2006
The FDA have revised the prescribing information for aprotinin (Trasylol).
FDA and Bayer Pharmaceuticals notified healthcare professionals of revisions to the prescribing information for Trasylol. The new labeling has a more focused indication, a new Warning that Trasylol administration increases the risk of renal dysfunction and may increase the need for dialysis in the perioperative period, and stronger warnings about anaphylactic reactions. In addition, due to the higher risk for anaphylactic reactions, re-administration of Trasylol to patients with a known or suspected exposure during the past 12 months is contraindicated.
admin October 24th, 2006
The American Association of Oral and Maxillofacial Surgeons have produced a position paper on Bisphosphonate-Related Osteonecrosis of the Jaws. The paper gives an overview of the risks, possible risk factors, and management strategies for the condition.
Link Here. [PDF 104kb]
[Via Reactions]
admin March 27th, 2006
A recent article in in Neurology (Rucker JC et al. Linezolid-associated toxic optic neuropathy. Neurology 2006;66:595-598) reported three cases of linezolid-induced optic and peripheral neuropathy associated with Linezolid. The author of the piece is quoted at this Medscape article:
“It appears that there is an association, but these side effects still seem to remain pretty rare,” Dr. Janet Rucker, from the Rush University Medical Center, in Chicago, told Reuters Health. “Linezolid is important to treat chronic and recurrent bacterial infections, so our objective is to educate the audience to recognize these possible side effects.”
Treatment of gram-positive bacterial infections with linezolid is recommended for a maximum of 28 days. However, “it is not uncommon to have patients on the medication for longer periods,” said Dr. Rucker.
Concerns have recently been raised about linezolid possibly inducing different types of neuropathies when administered for several months.
Dr. Rucker and colleagues describe three patients being treated linezolid for 5 to 10 months who developed painless, progressive visual loss. Examinations suggested metabolic optic neuropathies. After ruling out hereditary or nutritional causes, the team concluded that the symptoms were a possible toxic effect of linezolid.
When linezolid treatment was discontinued, the patients’ vision improved significantly within a month.
The team also analyzed clinical data from nine previously reported cases — patients who had developed visual symptoms after 5 to 11 months of linezolid therapy. These provided similar findings.
Pfizer, after discussion with the MHRA, have issued a letter (not available on-line) to healthcare professionals concerning Zyvox (linezolid) and the risks associated with its long-term use and also amended the Summary of Product Characteristics. They re-enforce that the recommended treatment duration for these conditions is 10-14 consecutive days, with a maximun treatment duration of 28 days. They advise that the safety and efficacy of linezolid has not been established when administered for periods longer than 28 days. On the subject of the rare cases of peripheral neuropathy and/or optic neuropathy Pfizer say:
We estimate that since its launch in 2000, over one million patients have been treated with linezolid worldwide. While it is not possible to establish an incidence rate for these adverse reactions due to inherent limitations of spontaneous reporting, such cases have been reported rarely. Of the optic neuropathy cases with known outcomes, three-quarters reported recovery. A quarter of cases progressed to vision loss and of those with known outcomes, half reported recovery. Of the peripheral neuropathy cases with known outcomes, a third reported complete or ongoing recovery.
The updated Summary of Product Characteristics for Zyvox (linezolid) is here.